Evidence map›Paper›PMID 39173480›Full record

ArticleTranslational oncology2024

GTF2H5 Identified as a crucial synthetic lethal target to counteract chemoresistance in colorectal cancer.

Junjie Nie, Xinwei Liu, Mu Xu, Xiaoxiang Chen, Shangshang Hu, Xinliang Gu, Huiling Sun, Tianyi Gao, Yuqin Pan, Shukui Wang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Junjie NieGeneral Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, Jiangsu, China.
Xinwei LiuGeneral Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, Jiangsu, China.
Mu XuGeneral Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, Jiangsu, China.
Xiaoxiang ChenGeneral Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, Jiangsu, China.
Shangshang HuGeneral Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, Jiangsu, China.
Xinliang GuGeneral Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, Jiangsu, China.
Huiling SunGeneral Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, Jiangsu, China.
Tianyi GaoGeneral Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, Jiangsu, China.
Yuqin PanGeneral Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, Jiangsu, China. Electronic address: panyuqin01@163.com.
Shukui WangGeneral Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, Jiangsu, China; Jiangsu Collaborative Innovation Center on Cancer Personalized Medicine, Nanjing Medical University, Nanjing 210000, Jiangsu, China. Electronic address: sk_wang@njmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSynthetic lethality (SL) emerges as a novel concept being explored to combat cancer progression and resistance to conventional therapy. Despite the efficacy of chemotherapy in select cases of colorectal cancer (CRC), a substantial proportion of patients encounter challenges, leading to an adverse prognosis of CRC patients. CRC-related SL genes offer a potential avenue for identifying therapeutic targets.

methodsCRC-related SL genes were obtained from the SynLethDB database. The bulk RNA sequencing data, mutation data, and clinical information for treated and untreated CRC patients were enrolled from the UCSC and GEO databases. The Tumor Immunology Single Cell Center database served as the repository for collecting and analyzing single-cell RNA sequencing data. The synergistic killing effect of SL genes and chemotherapeutic drugs on resistant cells was experimentally verified.

resultsIn the present study, pivotal SL genes associated with chemoresistance identified by using WGCNA and CRC patients categorized into two groups based on these genes. Variations between the groups were most pronounced in pathways associated with extracellular matrix remodeling. Further by integrating mutation data, five potential SL genes were discerned, which were highly expressed in the presence of TP53 or KRAS mutations, leading to a severely poor prognosis. Subsequent time series analysis revealed that the expression of GTF2H5 was gradually elevated at different stages of the transition from sensitive to resistant in CRC cells. Finally, it was preliminarily verified by experiments that GTF2H5 may play a key role in driving the drug-resistant transition within CRC cells.

conclusionsThe identification of SL genes that collaboratively interact with chemotherapeutic agents could provide new insights into solving the issue of chemotherapy resistance in CRC patients. And GTF2H5 wields a fundamental influence in inducing chemoresistance in CRC, which provided a potential therapeutic target for CRC.

Indexed as

3D co-culture systemChemoresistanceFOLFOXGTF2H5Synthetic lethality

Identifiers

PMID39173480
PMCPMC11382125

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.